Pneumocystis carinii is a major pathogen of patients with human immunodeficiency virus infection. The immune responses to P. carinii are poorly under-stood, but cytokines may play a role in both clearing P. carinii infection and in the hypoxia associated with P. carinii pneumonia that may be exacerbated following initiation of therapy. We have completed a study with Dr. Vogel examining the effects of interleukin-12 (IL-12) in SCID mice with P. carinii pneumonia. In this model no effect on P. carinii pneumonia was seen when IL-12 was administered either at the time of exposure to P. carinii or 4 weeks after exposure. We have begun studies to examine the role of the major surface glycoprotein in inducing protective immune responses in mice. In the future, we plan to use the SCID mouse model as well as other immunodeficient mice to evaluate further the role of indivi-dual cytokines and other immunoregulatory molecules in modulating P. carinii infection. It is hoped that these studies will provide insights into the role of cytokines in P. carinii pneumonia and may provide mechanisms for increasing clearance or decreasing the inflammation that may be causing hypoxia.